PROJECT SUMMARY The 2018 NIA - Alzheimer's Association Research Framework [AT(N)] for Alzheimer's Disease (AD) provides a biological context for studying AD by incorporating state-of-the art biomarkers of amyloid (A), tau (T) and neurodegeneration (N). Despite the fact that these biomarkers vary by race/ethnicity, no prior work has systematically examined them among Mexican Americans. Given that (1) Hispanic/Latinos are projected to experience the largest growth in AD and Alzheimer's Disease Related Dementias (ADRDs) by 2060 and (2) Mexican Americans are the largest segment of the U.S. Hispanic/Latino population, there is a pressing need to study prevalence, progression and clinical impact of these biomarkers among this underrepresented group. This work addresses goals of the National Alzheimer's Project Act (NAPA), NIA Milestones for AD and ADRD research, and needs highlighted by the AT(N) framework publication. The current research team consists of leading experts in Mexican American cognitive aging, neuroimaging (PET and MRI), blood-based biomarkers as well as advanced statistical modeling. By leveraging the ongoing HABLE cohort, infrastructure and data, we will test the following Specific Aims: Aim 1: Examine the prevalence, progression and clinical impact of cerebral markers of the 2018 AT(N) framework among community-dwelling Mexican Americans. Aim 2. Examine the prevalence, progression and clinical impact of blood markers of the 2018 AT(N) framework among community-dwelling Mexican Americans. Aim 3: To determine if blood-based biomarkers of A?40, A?42, tau and NfL can be used to screen for AT(N)-defined preclinical AD, prodromal AD and AD dementia for enrollment of Mexican Americans into novel clinical trials. The current study is highly significant for several reasons: (1) This is the first-ever large-scale multi-ethnic study of the AT(N) biomarkers, which is of tremendous importance given the racial/ethnic make-up of the U.S. population; (2) this work directly addresses goals set forth by NAPA as well NIA-Milestones for AD/ADRD science; (3) it will determine if ethnic-specific biomarker trajectories are appropriate and finally, (4) it will generate data and methods for increasing enrollment of Hispanics into clinical trials across the AT(N)-defined spectrum of AD (primary, secondary and tertiary prevention) beginning in primary care settings.